A case of High Dose Steroids and Pulmonary Nodules. Adrian Tramontana Western Health

Transcription

1 A case of High Dose Steroids and Pulmonary Nodules Adrian Tramontana Western Health

2 45 year old immunocompromised man admitted with septic pulmonary emboli in March 2014 Footer Text 2

3 Background History FSGS, Interstitial nephritis, ATN Dx on biopsy Dec 2013 Nephrotic range proteinuria moderate chronic renal parenchymal injury Rx Prednisolone 25 mg tds steroid induced diabetes DVT/ PE Feb 2014 Factor V Leiden 6/2/14 - R leg DVT Started Warfarin 12/2 - R basal subsegmental PE on V/Q IVC filter isnerted Footer Text 3

4 Background History Hypertension Dyslipidaemia Gout Footer Text 4

5 History Presented 7/3/14 General malaise and fatigue for 3 weeks lump in Right axilla 1 week Pimple that grew into an painful and tender lump left sided pleuritic chest pain with dyspnoea 1 dy Feeling hot and cold Polyuria and polydipsia Footer Text 5

6 Examination P-75, 125/85, R 16, sats 97% on 3L O2, afebrile 3cm tender erythematous abscess R upper arm Chest scattered crackles throughout Bilateral oedema to knees Footer Text 6

7 Investigations FBE 16.6/ 16.5/ 125 neut 14.4 UEC Cr 157, egfr 45 LFTs bili 8, ALP 215, GGT 177, ALT 55, Alb 16 INR 1.7 Ck 67 Protein electrophoresis Inflammatory response with low IgG 1.5 g/l Footer Text 7

8 Footer Text 8

9 Initial Management Initial Antibiotics in Emergency Ceftriaxone and Azithromycin Vancomycin I + D abscess on right arm Footer Text 9

10 Footer Text 10

11 Microbiology Results 7/3/14 Blood cultures negative 8/3/14 Axillary Swab Large polymorphs, Large numbers of GPC, Large numbers of GPB resembling diptheroids Growth mixed skin flora Footer Text 11

12 Microbiology Results BC from 8/3/15 After 3 days incubation Footer Text 12

13 Footer Text Photo Courtesy Jenny Wong Dorevitch Pathology 13

14 Footer Text 14

15 Blood Culture Isolate Nocardia farcinica Cotrimoxazole S Linezolid S Augmentin S Ceftriaxone R Minocycline I Tobramycin - R Imipenem - I Amikacin - S Ciprofloxacin - R Clarithromycin - R Footer Text 15

16 Treatment Bactrim DS Imipenem 500mg q8hrly CT brain no abscess Weaning of prednisolone 17/3 37.5mg 2/4 10mg daily 19/6/ Ceased Footer Text 16

17 Complications Psoas haematoma Requiring embolisation Seizure no CNS involvement on CT brain Footer Text 17

18 Progress 4 April Responding to Treatment Sensitivities Preliminary sensitivities Imipenem dose increased to 1g q8hrly 4 weeks total Rx Bactrim rash 13/5/14 Augmentin started 15/5/14 Rash in June with lip swelling and blistering on hands June 30 Rpt CT chest resolution of nodules 14 weeks Rx completed Footer Text 18

19 Progress? Rash due to scabies as wife also had rash 14/7/15 Rx scabies with invermectin and permethrine Minocycline 100mg bd Rx until 24/11/14 Footer Text 19

20 Nocardia Ubiquitous environmental bacteria Found in Soil, Decomposing Vegetation, other Organic Matter, Fresh and Salt Water. Footer Text 20

21 Taxonomy Sub-order aerobic Actinomycetes Includes Mycobacterium, Corynebacterium, Gordona, Tsukamurella Family Nocardiaceae Includes Nocardia and Rhodococcus Nocardia asteroides later named Nocardia asteroids complex now multiple species Footer Text 21

22 Microbiology Aerobic gram positive bacteria Filamentous bacteria hyhaelike branching on direct microscopy Varying degress of Acid Fastness Depending on mycolic acid composition in the cell wall Modified Kinyoun stain 1% sulphuric acid as decolorizer instead of HCl acid in ZN Beaded Acid fast bacilli compared to Mycobacteria Resemble Actinomyces on gram stain Actinomyces NOT acid fast Footer Text 22

23 Risk factors for infection Corticosteroids Cell Mediated Immune Deficits Solid organ transplant 0.6% to 3% Anti TNFα therapy Chronic Lung Disease particularly with steroid use 1/3 not immunocompromised eg. Traumatic cutaneous inoculation Footer Text 23

24 Footer Text 24

25 Clinical Presentation Wide spectrum Acute presentations fever leukocytosis 54% Chronic presentation Symptoms of organ involvement Not always present Pulmonary Pleural involvement with chest pain frequent Cutaneous abscess useful clue Can resemble lung Ca, fungal and mycobacterial infections Footer Text 25

26 Sites of Diseases Pulmonary via inhalation Contiguous spread pleura, pericardium, mediastinum, vena cava Can resemble actinomyces Haematogenous spread CNS 20-50% Extra-pulmonary Abscess formation chronic granulomatous inflammation Primary cutaneous nocardiosis direct implantation from soil Resembling Staph and Strep abscesses although more indolent Localised Cellulitis Sporotichoid like Nodules Footer Text 26

27 Discrete Pulmonary Nodules 62% May also be spiculated Footer Text 27

28 Cavitation of Pulmonary Nodules 40% Footer Text 28

29 Consolidation 54% Footer Text 29

30 Lung Cancer like presentation Footer Text 30

31 Pleural effusion/ Empyema 40% Aspirates often yield straw coloured fluid. Footer Text 31

32 Inhalation versus Haematogenous Inoculation Footer Text 32

33 Inhalation versus Haematogenous Inoculation Footer Text 33

34 Brain Abscess Single or multiple Footer Text 34

35 Wide spectrum of sites of Dissemination Footer Text 35

36 Co-Infections Sputum Culture H influenzae A fumigatus x 3 Nocardia cyriacigeorgica x2

37 Co-Infections Concomitant bacteraemia up to 63% in pulmonary infections Gram negative P. aeruginosa, others Gram Positive S. aureus Candida Other co-infections Fungal Aspergillus, Histoplasma CMV TB 21% of pulmonary infections in one study from Taiwan Non-Tuberculous Mycobacteria Footer Text 37

38 Differential Diagnosis versus Coinfections Footer Text 38

39 Nocardia bacteraemia 64% have pulmonary nocardiosis 28% concurrent cutaneous nocardiosis 19% CNS disease Can be radiologically occult post mortem finding in 1 case report Cases related to infected intravascular devices CVC and AVR Mortality better for subacute presentations (>4 weeks of symptoms) Blood Culture isolates may be contaminant (particularly in newborns) Footer Text 39

40 Nocardia Species Likely Geographic variation Pulmonary and Disseminated Disease N. asteroides Pulmonary and CNS N. farcinica Pulmonary and blood N. nova Peleg study of Tx patients on bactrim prophylaxis Isolated Cutaneous Disease N. Basiliensis Footer Text 40

41 Antimicrobial Susceptibility pattern Footer Text 41

42 Treatment Agents Used Bactrim 10mg/kg higher dose often used in CNS and disseminated disease Minocycline Imipenem/ Meropenem Ceftriaxone Linezolid Amikacin Footer Text 42

43 Mouse model of Bactericidal Effect Footer Text 43

44 Treatment No RCT evidence from case series no regimen demonstrated to be clinically superior Combination therapy Not superior to monotherapy in case series Provides increased coverage whilst awaiting sensitivities Bactrim + imipenem - widely used for CNS/ disseminated Imipenem + amikacin Linezolid + meropenem Bactrim + ceftriaxone Footer Text 44

45 Treatment Time to improvement usually 7-10 days Duration of Antibiotic therapy Skin 1-3 months unless mycetoma Pulmonary 4-6 weeks intravenous 6 months total Disseminated, CNS and ongoing immunosuppression 12 months + Footer Text 45

46 Treatment Additional management Source control Drainage of abscesses Removal of infected prosthesis eg CVC, AVR Reduce immunosuppression Footer Text 46

47 Effect of Reducing Immunosuppression Patient Initially refused treatment Anti-TNFα ceased 2 months and methotrexate 1 week before presentation Prednisolone 5mg

48 Summary Risk factors for Nocardia High dose steroid and impaired cell mediated immunity Clinical features to suspect Nocardia pulmonary infection + skin abscesses Imaging features Nodules +/- cavitation, Consolidation +/- Cavitation Pleural effusions/ empyema Co-infections common Treatment poorly defined Footer Text 48